Cannabinoids are terpenophenolic compounds found in Cannabis sativa, an annual plant belonging to the Cannabaceae family. The plant contains more than 400 chemicals and approximately 70 cannabinoids. The latter accumulate mainly in the glandular trichomes. The most active of the naturally occurring cannabinoids is tetrahydrocannabinol (THC), which is used for treating a wide range of medical conditions, including glaucoma, AIDS wasting, neuropathic pain, treatment of spasticity associated with multiple sclerosis, fibromyalgia and chemotherapy-induced nausea. THC is also effective in the treatment of allergies, inflammation, infection, epilepsy, depression, migraine, bipolar disorders, anxiety disorder, drug dependency and drug withdrawal syndromes.
Additional active cannabinoids include cannabidiol (CBD), an isomer of THC, which is a potent antioxidant and anti-inflammatory compound known to provide protection against acute and chronic neuro-degeneration. CBD is also used as an antiemetic to control nausea and as an apetite suppressant. In addition, CBD is used for the treatment of epilepsy, schizophrenia and Dravet's syndrome and recent studies suggest therapeutic for treating Alzheimers disease (AD).
Recent studies have shown that CBD converts to THC when exposed to heat or brought in contact with an acid. For instance, oral administration of CBD causes the acid catalyzed cyclization of CBD to THC in gut. The conversion of CBD to THC has limited its use as a therapeutic from the treatment of epilepsy, particularly, in pediatric patients.
The present invention provides methods to prevent the conversion of CBD to THC. Disclosed therefore are methods for synthesizing stable CBD derivatives. The inventive CBD derivatives do not readily convert to THC. Also described are CBD derivatives that are more favorably transported across the blood brain barrier (BBB), permitting an increased therapeutic concentration of CBD or its derivatives in the central nervous system (CNS).